A patient has been identified whose plasma mediates breakdown (presumably proteolysis) of normal von Willebrands factor (vWF). Proteolysis of vWF normally occurs through the action of a plasma enzyme that has recently been characterized; it accounts for the small quantities of cleavage products normally present in the circulation. Other enzymes, such as plasmin and leukocyte elastase, also can cleave vWF. Preliminary studies of this patients plasma have shown that there appear to be differences in cation and pH requirements of the patients enzyme when compared with the previously characterized enzyme. Further purification is being performed to better characterize the activity. We have developed a better and more rapid assay to evaluate the cleavage of vWF multimers and have characterized the dose response (rough quantitation of the enzyme in the patients plasma).During the past 9 months, we have developed a collagen-binding assay for the "normal" vWF protease, and have established preliminary steps for purification of this enzyme using an affinity chromatography step, as well as more routine plasma fractionation steps. We are also taking steps to set up a collaboration in order to obtain patient plasmas for testing as a special clinical laboratory test.